Multiple gastrointestinal stromal tumors with novel germline c- kit gene mutation, K642T, at exon 13

• Published in: Human pathology 2014-04, Vol.45 (4), p.884-888
• Main Authors: Yamanoi, Kazuhiro, MD, PhD, Higuchi, Kayoko, MD, Kishimoto, Hirofumi, MD, Nishida, Yasunori, MD, Nakamura, Masato, MD, PhD, Sudoh, Motohiro, MD, Hirota, Seiichi, MD, PhD
• Format: Article
• Language: English
• Subjects: DNA Mutational Analysis; Exon 13; Exons - genetics; Familial; Female; Gastrointestinal Stromal Tumors - genetics; Gastrointestinal Stromal Tumors - pathology; Germ-Line Mutation; Germline mutation; GIST; Heterotopic ossification; Humans; Immunohistochemistry; Middle Aged; Pathology; Proto-Oncogene Proteins c-kit - genetics; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2013.11.009

Summary Multiple gastrointestinal stromal tumors (GISTs) caused by germline c- kit gene mutations are an extremely rare autosomal dominant disorder. A 57-year-old Japanese woman was referred to a hospital for appetite loss and severe weight loss. She had 2 large abdominal masses around the stomach, which were surgically resected. Histological examination revealed that these tumors were GISTs. Multiple microscopic GISTs and diffuse hyperplasia of the interstitial cells of Cajal were also seen in the background gastric and small intestinal walls. Characteristically, the GISTs showed severe hyalinization with calcification and partial heterotopic ossification, which may have caused the patient’s severe dysphagia. Mutational analysis of the c- kit gene revealed a substitution at codon 642 in exon 13 (K642T) in the tumor, normal ileal mucosa and peripheral blood leukocytes, indicating that the mutation is in the germline. This is the first case of multiple GISTs with novel germline c- kit gene mutation at exon 13.